Alzheimer’s disease is characterised by so-called plaques – white clumps of the beta-amyloid protein in the brain. The prevailing line of argument has therefore been that patients should be treated to make the plaques disappear. This approach sounds logical, but has not resulted in any new effective medicines – and Professor of Experimental Neurology, Gunnar Gouras, thinks it could be wrong.

His latest research finding indicates that it could more meaningful to stabilise the nerve cells’ beta-amyloid than to try to remove the protein. This is a different angle and deviates from most of the research in the area. But, such an approach can be necessary sometimes, argues Gunnar Gouras:

“We must think outside the box and be open to new possibilities. None of the trials using new drugs targeting beta-amyloid have made patients better – one trial even made them worse”, he says.

The work that led to the surprising discovery was conducted by a researcher in his group, Oxana Klementieva, at MAX Lab. This is the now disused predecessor to the large synchrotron radiation facility, MAX IV, where material is studied using electrons accelerated to high speeds.

Gunnar Gouras considers it a strength that such facilities are at the University, as they give researchers from all disciplines the opportunity to conduct studies that cannot be done using their ordinary methods. The MAX study also provided a picture of a stage that could not previously be seen in the brain – the stage before the build-up of plaques in Alzheimer’s disease. The images showed there was a preliminary stage in which the beta-amyloid protein underwent structural changes.

Further studies using other methods showed that the protein did not, as was previously thought, constitute a monomer (a solitary molecule), but a tetramer (a unit of four linked molecules).

Gunnar Gouras and his colleagues thought this was very interesting, as there is a rare neurological disease called transthyretin amyloidosis, in which a similar connection between four molecules plays an important role.

In this case, it is known that the linked tetramers are not the cause of the disease. On the contrary, the disease is associated with what happens if the tetramers fall apart. If the tetramers stabilise and do not fall apart, the course of the disease can be slowed, and such an anti-retroviral medicine actually exists.

The same principle could also apply to beta-amyloid in Alzheimer’s disease: a substance that stabilises the tetramers of beta-amyloid would perhaps act like a medicine.“It’s a new approach that could be worth testing. After all, there is so much we still don’t know about the brain. Perhaps we need beta-amyloid, so would we be doing ourselves a bad turn if we actually got rid of the protein?” wonders Gunnar Gouras.

In addition to conducting his own research on Alzheimer’s disease, he is also the coordinator of the Multi-Park research area. The vice-coordinator is Oskar Hansson, who studies, among other things, biomarkers for the early diagnosis of Alzheimer’s and Parkinson’s. He collaborates closely with Gunnar Gouras, who has actually moved down one floor in the BMC building, one reason being that their laboratories would be next to each other.

Multi-Park is an interdisciplinary network of researchers who work on both Parkinson’s disease and related neurodegenerative diseases. Its two leaders are more oriented towards Alzheimer’s than Parkinson’s, but that does not affect the activities of the network, comments Gunnar Gouras:“In treatment terms, there is a considerable difference between the diseases, as there are medicines for Parkinson’s, but not for Alzheimer’s. But, in scientific terms the diseases are actually quite similar!” he explains.

One similarity is that abnormal build-up of proteins occurs in both cases, accumulations of alpha-synuclein and beta-amyloid respectively. Both these proteins, as well as the tau protein in Alzheimer’s, also seem able to move from cell to cell as a sort of internal “infectious agent” in the brain.

Another similarity is that the synapses – the links between the brain’s nerve cells – become less active in both diseases. Dementia is also a common consequence of Parkinson’s disease, and the patients who deteriorate faster have more Alzheimer’s-like characteristics in their dementia.

“There is a lot of overlap between the diseases and I believe that research will progress faster if we cooperate”, says Gunnar Gouras.

In the best of all possible worlds, his MAX IV discovery on the disintegration of tetramers as a preliminary stage in Alzheimer’s would already have been picked up by a pharmaceutical company. However, the major companies are like ocean liners – once they have set a course, it is very difficult to rapidly change direction.

And Gunnar Gouras himself does not have as much time to devote to the area as he would like. Even so, there will be a continuation of the research:“We want to see if tetramers are composed solely of beta-amyloid, or if other substances are present. If there are, these other substances could also represent treatment objectives”, he concludes.